Sodium hydride → HCID 178490880, compound

HRID 1370128Notes

Reaction equation

HRID 1370128 reaction equation
[OH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([N:8]2[C:12]3[CH:13]=[CH:14][C:15]([C:17]([F:20])([F:19])[F:18])=[CH:16][C:11]=3[NH:10][C:9]2=[O:21])[CH2:4][CH2:3]1.[H-].[Na+].[CH3:24][O:25][C:26]1[CH:27]=[C:28]([CH:31]=[CH:32][C:33]=1[O:34][CH3:35])[CH2:29]Br>CN(C)C=O>[CH3:24][O:25][C:26]1[CH:27]=[C:28]([CH:31]=[CH:32][C:33]=1[O:34][CH3:35])[CH2:29][N:10]1[C:11]2[CH:16]=[C:15]([C:17]([F:20])([F:18])[F:19])[CH:14]=[CH:13][C:12]=2[N:8]([C@H:5]2[CH2:6][CH2:7][C@H:2]([OH:1])[CH2:3][CH2:4]2)[C:9]1=[O:21]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 109004583,4-Dimethoxybenzyl bromideHCID 178518626HCID 178518626, compound

Product 1

HCID 178490880HCID 178490880, compoundYield 72.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(trans-4-hydroxycyclohexyl)-5-trifluoromethyl-2,3-dihydro-1H-benzimidazol-2-one (200 mg) in anhydrous N,N-dimethylformamide (2 mL) was added portionwise sodium hydride (29.3 mg, 60% dispersion in mineral oil) at 5° C. under nitrogen atmosphere, and the mixture was stirred at room temperature for 30 minutes. After adding 3,4-dimethoxybenzylbromide (154 mg), the mixture was stirred at room temperature for 2 hours. The mixture was partitioned between ethyl acetate and water. The separated organic layer was washed successively with 1 N-hydrochloric acid, water, an aqueous saturated sodium hydrogencarbonate solution and brine. The organic layer was dried over magnesium sulfate and evaporated in vacuo. The residue was subjected to a preparative silica gel column chromatography eluting with 5% methanol in chloroform. The obtained amorphous was recrystallized from diethyl ether to give 3-(3,4-dimethoxybenzyl)-1-(trans-4-hydroxycyclohexyl)-5-trifluoromethyl-2,3-dihydro-1H-benzimidazol-2-one (217.9 mg) as a colorless solid.

Workup

  1. stirringthe mixture was stirred at room temperature for 2 hours
  2. customThe mixture was partitioned between ethyl acetate and water
  3. washThe separated organic layer was washed successively with 1 N-hydrochloric acid, water
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. customevaporated in vacuo
  6. washeluting with 5% methanol in chloroform
  7. customThe obtained amorphous was recrystallized from diethyl ether

Sources & evidence

ORD record
ord-982c26284dc94fa49fba65e0f10cc9cb
Source dataset
uspto-grants-2003_06
Patent number
US06582351B1

Reaction notes

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